New Product Slideshow
Venclexta (venetoclax)
Introduction
Brand name: Venclexta
Generic name: Venetoclax
Pharmacological class: BCL-2 inhibitor
Strength and Formulation: 10mg, 50mg, 100mg; tablets
Manufacturer: AbbVie
How supplied: Starting Pack—1 (four weekly blisters); Wallets 10mg—14; 50mg—7; Tabs 100mg—120
Legal Classification: Rx
VENCLEXTA
Indications
Chronic lymphocytic leukemia (CLL)
in patients with 17p deletion, as detected by an FDA-approved test, who have received at least 1 prior therapy
Dosage & Administration
Swallow whole
Take with food and water
Initially 20mg once daily for Week 1, then 50mg once daily for Week 2, then 100mg once daily for Week 3, then 200mg once daily for Week 4, then 400mg once daily for Week 5 and beyond until disease progression or unacceptable toxicity
Risk assessment/prophylaxis for tumor lysis syndrome or dose modifications for toxicities: see full labeling
Considerations for Special Populations
Pregnancy: Avoid
Nursing mothers: Not recommended
Pediatric: Not established
Geriatric: No overall differences in safety and efficacy
Hepatic impairment: Moderate to severe impairment: monitor closely
Renal impairment: Severe impairment or dialysis: no dose recommended
Warnings/Precautions
Risk of tumor lysis syndrome (esp. with high tumor burden, comorbidities, CrCl <80mL/min); perform tumor burden assessment, radiographic evaluation, blood chemistry; correct pre-existing abnormalities prior to initiation
Premedicate with anti-hyperuricemics and ensure adequate hydration
Monitor CBCs and for signs of infection; interrupt or reduce dose if severe neutropenia occurs
Warnings/Precautions
Embryo-fetal toxicity
Females of reproductive potential: should undergo pregnancy testing prior to initiation
Use effective contraception during and for ≥1 month after final dose
Interactions
See Contraindications
Concomitant strong CYP3A inhibitors after ramp-up phase (eg, ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, lopinavir, ritonavir, telaprevir, posaconazole, voriconazole); avoid use or reduce venetoclax dose by ≥75%
Interactions
Avoid concomitant moderate CYP3A inhibitors (eg, erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil) or P-gp inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, cyclosporine, felodipine, quercetin, quinidine, ranolazine, rifampin, ticagrelor); consider alternatives; if inhibitor necessary, reduce venetoclax dose by ≥50% and monitor closely
Interactions
Resume at prior venetoclax dose 2–3 days after discontinuing the inhibitor
Avoid concomitant strong CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort) or moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); consider alternatives
Avoid live attenuated vaccines until B-cell recovery
Interactions
Avoid grapefruit, Seville oranges, and starfruit during treatment
Monitor INR with concomitant warfarin
Avoid P-gp substrates with narrow therapeutic index (eg, digoxin, everolimus, sirolimus); if necessary, take ≥6hrs before venetoclax
Adverse Reactions
Neutropenia
Diarrhea
Nausea
Anemia
Upper respiratory tract infection
Thrombocytopenia
Fatigue
Mechanism of Action
Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2
It helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, triggering mitochondrial outer membrane permeabilization and the activation of caspases
In non-clinical studies, venetoclax demonstrated cytotoxic activity in tumor cells that overexpress BCL-2
Pharmacokinetics
Distribution: Highly bound to plasma protein
Metabolism: CYP3A4/5 (major)
Elimination: Fecal
Clinical Trials
The efficacy of Venclexta was established in an open-label, single-arm, multicenter trial (n=106) in patients with CLL with 17p deletion who had received at least 1 prior therapy
Patients received Venclexta via a weekly ramp-up schedule starting at 20mg and ramping to 50mg, 100mg, 200mg, and finally 400mg once daily until disease progression or unacceptable toxicity
Clinical Trials
The efficacy of Venclexta was evaluated by overall response rate (ORR) as assessed by an Independent Review Committee (IRC) using the updated NCI-WG guidelines
The median time on treatment at the time of evaluation was 12.1 months
Clinical Trials
ORR was seen in 80.2% of patients (95% CI: 71.3, 87.3) treated with Venclexta
Complete remission was seen in 5.7% of patients and complete remission with incomplete marrow recovery was seen in 1.9% of patients
Nodular partial remission was seen in 2.8% of patients
Partial remission was seen in 69.8% of patients
Clinical Trials
The median time to first response was 0.8 months (range 0.1–8.1 months)
For patients who achieved complete remission or complete remission with incomplete bone marrow recovery, 3% were minimal residual disease (MRD) negative in the peripheral blood and bone marrow
For more clinical data, see full labeling
New Product Monograph
For more information view the product monograph available at:
http://www.empr.com/venclexta/drug/34571/
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